Recent evidence suggests that at least two motor pathways can activate the pattern generator for rhythmic mastication. The neurochemistry of these pathways is just beginning to be explored. One pathway, the corticotrigeminal tract, can be inhibited by serotonin agonists. The other, an extrapyramidal pathway, is activated by dopamine agonists and depends upon an intact superior colliculus. This extrapyramidal pathway can also be activated by electrical stimulation of the rabbit tooth pulp and inhibited by opiate agonists. The purpose of this proposal is to examine the effects of acetylcholine, an neurotransmitter hypothesized to be present in the extrapyramidal masticatory pathway. A further aim is designed to demonstrate that acetylcholine, in fact does exert its effects on mastication by way of the extrapyramidal pathway. Finally, the proposed work aims to show the sequence of action of acetylcholine with respect to that of transmitters known to mediate the extrapyramidal pathway of mastication. In addition to the improved understanding of the mechanisms underlying mastication gained from elucidating the role of neurotransmitters, this line of research is likely to lead to the development of pharmacological approaches to treatment of oral parafunction. Naive New Zealand white rabbits will be the subjects of all experiments. In order to determine whether ACh itself is sufficient to produce mastication the cholinergic agent physostigmine will be injected intravenously into 15 rabbits. The presence of rhythmic mastication will be observed and verified by surface EMG recordings of the masseter and digastric muscles. The next aim is to determine whether the role of acetylcholine in inducing mastication is mediated via the extrapyramidal pathway. To do this a muscarinic cholinergic antagonist will be used to inhibit electrical tooth pulp stimulation-induced mastication in 15 anesthetized rabbits and compared with 15 anesthetized controls. Three rabbits will be used to verify the proper dosage of antagonist and prove that physostigmine exerts its effects via ACh activity. The final two specific aims are designed to determine the sequence of action of ACh with respect to two other extrapyramidal neurotransmitters namely dopamine and opiates. These aims will be accomplished by attempting to block ACh induced mastication using a selective dopamine antagonist and an opiate agonist in 15 rabbits each